SA-X from Metroid Fusion. She scared the shit out of me which is an impressive feat given that:

A) It was just a Gameboy Advance game
B) She never said a word

Just a ruthless alien that spent the entire game stalking and hunting you, and sure as hell destroyed you if you were ever seen.

"It hath been found by experience that no matter how decent, intelligent or thoughtful the reasoning of a conservative may be, as an argument with a liberal is advanced, the probability of being accused of ‘bigotry’, ‘hatred’ or ‘intolerance’ approaches 1." - Cranmer's Law

Lots of love for Kefka here. I approve. Definitely my favourite villain. Apart from his delightful personality, awesome laugh and great development throughtout the game, he's one of if not the most quotable game character I've ever seen.

Doesn't hurt that Dancing Mad is one of the best pieces of video game music ever, either.

Sovereign is a personal favourite, too. The first time you talk to him on Virmire is one of the most awesome moments I've experienced in a game. Always liked him (it?) more than Harbinger, too. Thought they messed up the Reaper voices in ME2 and ME3.

Also, every unimaginable cosmic horror and eldritch abomination. Pure evil villains that don't want to rule, conquer or have revenge get bonus points from me. Absoulte and total annihilation of the universe is the only worthy goal. Fuck the misunderstood crybaby villains with mommy issues.

I was trying to think of some newer ones, but I guess nostalgia doesn't make them like they used to. : \ The reapers in general were pretty awesome bad guys.

Also I hate to say it, but Sephiroth was actually a pretty awesome bad guy. He's just so totally overhyped it's hard to admit it now. He gets a free pass from being total emobait because he was around before emo was a thing.

Seymour, never have I wanted to beat the living snot out of a fictional character as much as him.
Special mentions go to Pyramid Head, for being the embodiment of pure evil; Kane, for being a cocky as hell badass; Glados, for comedy value; and the black car from Ridge Racer.

Pyramid Head from Silent Hill 2 easily wins for best antagonist in my book (With an honorable mention for Majora from Majora's Mask). But for an antagonist that I TRULY felt hatred toward was Kai Leng from Mass Effect 3...such a pompous little ass.